Immune boosting by B.1.1.529 (Omicron) depends on previous SARS-CoV-2 exposure
Catherine J. Reynolds,Corinna Pade,Joseph Gibbons,Diana Munoz Sandoval,George Joy,Nasim Forooghi,Charlotte Manisty,James C. Moon,Rosemary J. Boyton,Hakam Abbass,Aderonke Abiodun,Mashael Alfarih,Zoe Alldis,Daniel M. Altmann,Oliver E. Amin,Mervyn Andiapen,Jessica Artico,João B Augusto,Georgina L Baca,Sasha N. L. Bailey,Anish N Bhuva,Alex Boulter,Ruth Bowles,Olivia V Bracken,Ben O’Brien,Tim Brooks,Natalie Bullock,David Butler,Gabriella Captur,Olivia Carr,Nicola Champion,Carmen Chan,Aneesh Chandran,Tom Coleman,Jorge Couto de Sousa,Xose Couto-Parada,Eleanor Cross,Teresa Cutino-Moguel,Silvia D'Arcangelo,Rhodri H Davies,Brooke Douglas,Cecilia Di Genova,Keenan Dieobi-Anene,Mariana O. Diniz,Ana Gabriela Aguilar Ellis,Karen Feehan,M. Finlay,Marianna Fontana,Sasha Francis,David Gillespie,Derek W. Gilroy,Matt Hamblin,Gabriella Harker,Georgia C. Hemingway,Jacqueline Hewson,Wendy E. Heywood,Lauren M. Hickling,Bethany Hicks,Aroon D. Hingorani,Lee Howes,Ivie Itua,Victor Jardim,Wing-Yiu Jason Lee,Melanie Jensen,Jessica Jones,Meleri Jones,V. S. Kapil,Caoimhe Kelly,H. Kurdi,Jonathan Lambourne,Kai-Min Lin,Siyi Liu,Aaron Lloyd,Sarah Louth,Mala K. Maini,Vineela Mandadapu,Áine McKnight,Katia Menacho,C. Mfuko,Kevin Mills,Sebastian Millward,Oliver Mitchelmore,Christopher William Moon,Sam M. Murray,Mahdad Noursadeghi,Ashley Otter,Susana Palma,Ruth Parker,Kush Patel,Mihaela Pawarova,Steffen E. Petersen,Brian Piniera,Franziska P Pieper,Lisa Rannigan,Alicja Rapala,Amy Richards,Matthew Robathan,Joshua Rosenheim,Cathy Rowe,M Royds,Jane Sackville West,Genine Sambile,Nathalie Schmidt,Hannah Selman,Amanda Semper,Andreas Seraphim,Mihaela Simion,Angelique Smit,Michelle Sugimoto,Leo Swadling,Stephen Taylor,Nigel J. Temperton,Stephen Thomas,George Douglas Thornton,Thomas A. Treibel,Arthur Tucker,A. Varghese,Jessry Veerapen,Mohit Vijayakumar,Time Warner,Sophie Welch,Hannah White,Theresa Wodehouse,Lucinda Wynne,Dan Zahedi,Benjamin M. Chain +125 more
TLDR
B and T cell immunity against previous variants of concern was enhanced in triple vaccinated individuals, but magnitude of T and B cell responses against B.1.1 .1.529 spike protein was reduced.Abstract:
The Omicron, or Pango lineage B.1.1.529, variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) carries multiple spike mutations with high transmissibility and partial neutralizing antibody (nAb) escape. Vaccinated individuals show protection against severe disease, often attributed to primed cellular immunity. We investigated T and B cell immunity against B.1.1.529 in triple BioNTech BNT162b2 messenger RNA–vaccinated health care workers (HCWs) with different SARS-CoV-2 infection histories. B and T cell immunity against previous variants of concern was enhanced in triple-vaccinated individuals, but the magnitude of T and B cell responses against B.1.1.529 spike protein was reduced. Immune imprinting by infection with the earlier B.1.1.7 (Alpha) variant resulted in less durable binding antibody against B.1.1.529. Previously infection-naïve HCWs who became infected during the B.1.1.529 wave showed enhanced immunity against earlier variants but reduced nAb potency and T cell responses against B.1.1.529 itself. Previous Wuhan Hu-1 infection abrogated T cell recognition and any enhanced cross-reactive neutralizing immunity on infection with B.1.1.529. Description Importance of infection history A long-term study of healthcare workers in the United Kingdom has allowed their history of infection and vaccination to be traced precisely. Reynolds et al. found some unexpected immune-damping effects caused by infection with a heterologous variant to the latest wave of infection by the Omicron/Pango lineage B.1.1.529. The authors found that Omicron infection boosted immune responses to all other variants, but responses to Omicron itself were muted. Infection with the Alpha variant provided weaker boosting for Omicron-specific responses. Furthermore, Omicron infection after previous Wuhan Hu-1 infection failed to boost neutralizing antibody and T cell responses against Omicron, revealing a profound imprinting effect and explaining why frequent reinfections occur. —CA Omicron infection boosts immunity against early variants in infection-naive triple vaccinees, but less so after prior infection. INTRODUCTION B.1.1.529 (Omicron) and its subvariants pose new challenges for control of the COVID-19 pandemic. Although vaccinated populations are relatively protected from severe disease and death, countries with high vaccine uptake are experiencing substantial caseloads with breakthrough infection and frequent reinfection. RATIONALE We analyzed cross-protective immunity against B.1.1.529 (Omicron) in triple-vaccinated health care workers (HCWs) with different immune-imprinted histories of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during the ancestral Wuhan Hu-1, B.1.1.7 (Alpha), and B.1.617.2 (Delta) waves and after infection during the B.1.1.529 (Omicron) wave in previously infection-naïve individuals and those with hybrid immunity, to investigate whether B.1.1.529 (Omicron) infection could further boost adaptive immunity. Spike subunit 1 (S1) receptor binding domain (RBD) and whole spike binding, live virus neutralizing antibody (nAb) potency, memory B cell (MBC) frequency, and T cell responses against peptide pools and naturally processed antigen were assessed. RESULTS B and T cell recognition and nAb potency were boosted against previous variants of concern (VOCs) in triple-vaccinated HCWs, but this enhanced immunity was attenuated against B.1.1.529 (Omicron) itself. Furthermore, immune imprinting after B.1.1.7 (Alpha) infection resulted in reduced durability of antibody binding against B.1.1.529 (Omicron), and S1 RBD and whole spike VOC binding correlated poorly with live virus nAb potency. Half of triple-vaccinated HCWs showed no T cell response to B.1.1.529 (Omicron) S1 processed antigen, and all showed reduced responses to the B.1.1.529 (Omicron) peptide pool, irrespective of SARS-CoV-2 infection history. Mapping T cell immunity in class II human leukocyte antigen transgenics showed that individual spike mutations could result in loss or gain of T cell epitope recognition, with changes to T cell effector and regulatory programs. Triple-vaccinated, previously infection-naïve individuals infected during the B.1.1.529 (Omicron) wave showed boosted cross-reactive S1 RBD and whole spike binding, live virus nAb potency, and T cell immunity against previous VOCs but less so against B.1.1.529 (Omicron) itself. Immune imprinting from prior Wuhan Hu-1 infection abrogated any enhanced cross-reactive antibody binding, T cell recognition, MBC frequency, or nAb potency after B.1.1.529 (Omicron) infection. CONCLUSION Vaccine boosting results in distinct, imprinted patterns of hybrid immunity with different combinations of SARS-CoV-2 infection and vaccination. Immune protection is boosted by B.1.1.529 (Omicron) infection in the triple-vaccinated, previously infection-naïve individuals, but this boosting is lost with prior Wuhan Hu-1 imprinting. This “hybrid immune damping” indicates substantial subversion of immune recognition and differential modulation through immune imprinting and may be the reason why the B.1.1.529 (Omicron) wave has been characterized by breakthrough infection and frequent reinfection with relatively preserved protection against severe disease in triple-vaccinated individuals. Hybrid immune damping. (A) Triple-vaccinated HCWs with different SARS-CoV-2 infection histories show boosted cross-reactive immunity against VOCs, less so against Omicron. (B) Breakthrough infection during the Omicron wave boosts cross-reactive immunity in triple-vaccinated, previously infection-naïve individuals against VOCs, less so against Omicron itself; imprinting by previous Wuhan Hu-1 infection ablates Omicron immune boosting. (C) T cell recognition of Omicron mutation sequences is linked to altered transcription.read more
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Covid-19 Vaccine Effectiveness against the Omicron (B.1.1.529) Variant
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